tbuckley/cabot-search huggingface dataset:
Real-world data of use of nivolumab in platinum refractory head and neck cancers.
Authors: Jatin Choudhary, Hemanth Kumar, Madala Ravikrishna, Vijay Maruti Patil, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

e18686 Background: Nivolumab is one of the approved agents for platinum refractory and second line treatment in head and neck cancers as per NCCN guidelines. However, accessibility of nivolumab in low- and middle-income countries is less than 1-3%.There is data suggesting that low doses of nivolumab can also be effective. Hence in this analysis we explore the outcomes and adverse events with low doses of nivolumab in the second line and beyond setting. Methods: The head and neck medical oncology unit of Tata memorial hospital maintains a prospective database of all patients undergoing immunotherapy. A query was raised in this database to identify head and neck cancer patients who were treated with low doses of nivolumab. We identified 42 patients. The baseline characteristics, compliance to nivolumab, the reason for administration of low dose and the outcomes (progression free survival, date of progression, date of death) were recorded. The dose of nivolumab used in this study was 40 mg flat dose every 2 weeks. Descriptive statistics were performed. Kaplan Meier estimates were used to see overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 55.8 (IQR: 25.8-82.8) Male to female ratio was 53:11. All patients were platinum refractory and had progressive disease within the last 6 months of the last dose of platinum. The ECOG performance status was 0- 1 in 56 (88.9%) in patients and 2 in 8 (11.1%) patients. Median number of immunotherapy cycles received was 2 (1-4). The response was seen in 15 (23.1%) patients. The median OS was 6.7months (3.4-8.8) and PFS was 2.3 months (0.6-4.02) The details regarding PD L-1 expression and effectiveness of nivolumab will be presented at the conference. Conclusions: Low doses of nivolumab can be an option which is efficacious in patients who do not have access to standard dose nivolumab. There is a need for testing this regimen in large randomized studies as full doses of nivolumab are not accessible to the vast majority of the patients in low- and middle-income countries.
Comparison of clinical outcomes after phalloplasty with versus without urethral lengthening in transgender men
Authors: F.P.W. de Rooij, W.B. Van Der Sluis, B.L. Ronkes, T.D. Steensma, M. Al-Tamimi, R.J.A. Van Moorselaar, M-B. Bouman, G.L.S. Pigot
Journal: European Urology (2022)
Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus–response in spinal muscular atrophy
Authors: Chunchu Deng, Sebastian Reinhard, Luisa Hennlein, Janna Eilts, Stefan Sachs, Sören Doose, Sibylle Jablonka, Markus Sauer, Mehri Moradi, Michael Sendtner
Journal: Translational Neurodegeneration (2022)

Abstract Background Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These pathological changes do not only base on altered axonal and presynaptic architecture, but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic terminals. However, it remains enigmatic whether the ER and ribosome crosstalk is impaired in the presynaptic compartment of motoneurons with Smn (survival of motor neuron) deficiency that could contribute to axonopathy and presynaptic dysfunction in SMA. Methods Using super-resolution microscopy, proximity ligation assay (PLA) and live imaging of cultured motoneurons from a mouse model of SMA, we investigated the dynamics of the axonal ER and ribosome distribution and activation. Results We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient motoneurons. In addition, in axon terminals of Smn-deficient motoneurons, ribosomes failed to respond to the brain-derived neurotrophic factor stimulation, and did not undergo rapid association with the axonal ER in response to extracellular stimuli. Conclusions These findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases.
Multiple ipsilateral renal masses treated with robot-assisted partial nephrectomy: A multi-institutional series
Authors: A. Uleri, M. Paciotti, P. Diana, G. Lughezzani, M. Lazzeri, P. Casale, C. Bravi, L. Sarchi, A. Mottaran, S. Knipper, G. Naeyer, R. Groote, A. Mottrie, N. Buffi
Journal: European Urology (2022)
An Independent Seizure-Onset Zone in Medial Temporal Lobe Found by 18F-FDG PET Imaging Besides Epileptogenic Periventricular Nodular Heterotopia
Authors: Ruijie Guo, Liri Jin, Wanchen Dou, Linwen Liu, Ruixue Cui
Journal: Clinical Nuclear Medicine (2022)

A 23-year-old man with drug-resistant epilepsy was admitted for presurgical evaluation. The epileptogenic zone could not be derived from seizure semiology and scalp electroencephalographic monitoring definitely. MRI showed periventricular nodular heterotopia in occipital horn of left lateral ventricle with high FDG uptake on interictal 18 F-FDG PET scan, whereas the hypometabolic zone in the left medial temporal lobe was also found on PET with no abnormality on MRI. Stereoelectroencephalographic implantation was performed to identify the seizure-onset zone. Two independent epileptogenic foci located in periventricular nodular heterotopia and left hippocampus were validated by stereoelectroencephalographic monitoring and the outcome of subsequent thermocoagulation.
Sex dependence of hypothyroidism on malignant tumor growth.
Authors: Valeria A. Bandovkina, Elena M. Frantsiyants, Irina V. Kaplieva, Natalia D. Cheryarina, Ekaterina I. Surikova, Yulia A. Pogorelova, Alina Yu Arakelova, Ayna M. Salatova, Marina A. Engibaryan, Yulia V. Ulianova, Viktoriya L. Volkova, Dmitry A. Rozenko, Oleg I. Kit
Journal: Journal of Clinical Oncology (2022)

e23558 Background: Experimental data showed proliferative and anti-apoptotic effects of thyroxine (T4) and triiodothyronine (T3) on cancer cells which regulate gene expression and stimulate estrogen-like effects. The purpose of the study was to analyze effects of hypothyroidism on the development of malignant tumors in male and female rats. Methods: Female (n = 15) and male (n = 15) white outbred rats weighing 150 g and more received mercazolil (2.5 mg/100 g of weight) daily for 30 days (total dose of 75 mg/100 g of weight). Blood levels of T3, T4 and TSH were measured in all animals. When persistent hypothyroidism was observed, Guerin's carcinoma (GC, group 1) and sarcoma 45 (S45, group 2) were inoculated at a dose of 2 million cells in 0.5 ml of saline under the skin of the back to animals of both genders. The control group included rats of both genders with subcutaneous inoculation of Guerin's carcinoma and sarcoma-45 in the same dosage and volume but without preliminary reproduction of the hypothyroidism model. Results: Average tumor volumes in females with GC and hypothyroidism were less than in animals of the control group: after 4 days by 1.3 times (p &lt; 0.05), after 7 and 10 days by 1.4 times (p &lt; 0.05), after 14 days by 1.5 times (p &lt; 0.05), after 18 days by 1.3 times (p &lt; 0.05), and after 21 days by 1.4 times (p &lt; 0.05). The survival of female rats in the main group was 1.6 times higher (p &lt; 0.05) than in rats of the control group. Average tumor volumes in females with S45 and hypothyroidism were less than in animals of the control group: after 4 days by 1.4 times (p &lt; 0.05), after 7 and 10 days by 1.6 and 3.2 times (p &lt; 0.05), after 14 days by 3.9 times, and after 18 days by 4.8 times. The survival of female rats in the main group was 1.8 times higher (p &lt; 0.05) than in rats of the control group. Average tumor volumes in males of the main group with GC and hypothyroidism after 18 and 21 days were similar to the values in animals of the control group. Their survival did not differ from the survival of control males. Average tumor volumes in males of the main group with S45 and hypothyroidism after 10 and 21 days were similar to the values in animals of the control group. Their survival did not differ from the survival of control males. Conclusions: Hypothyroidism in female rats with GC and S45 inhibited the growth of malignant tumors and improved the survival of animals, while in males no such inhibiting effect was observed.
Profile and outcomes of patients with subsequent ovarian cancer diagnosis following a prior malignancy in the United States.
Authors: Oluwasegun Akinyemi, Faith Abodunrin, Tsion F Andine, Bolarinwa Akinwumi, Irene Akinyemi, Ademola Ojo, Christina Lipscombe, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e18541 Background: The relationship between a subsequent ovarian cancer and a prior malignancy is complex with possible etiological, genetic, and therapeutic implications. Little is known about the epidemiological and clinical profile of this category of patients. The aim of the present study is to determine the factors associated with the development of ovarian cancer as a subsequent malignancy after a prior malignancy from another organ and determinants of improved survival in these women. Methods: We utilized the SEER 18 Registry 1975-2016 to conduct a retrospective analysis of women who developed a second primary ovarian malignancy following a prior cancer diagnosis. The outcome of interest was the latency interval between the initial primary malignancy diagnosis and a subsequent ovarian cancer diagnosis. Utilizing the cox regression model, we determined the factors associated with the overall survival of these women. Results: There were 10, 800 women who subsequently developed ovarian cancers following a prior malignancy. The commonest prior malignancies were breast cancers (38.2%), endometrial cancers (23.7%), and colorectal cancers (9.5%). The latency interval from developing a subsequent ovarian malignancy was 6.8±6.3 yrs. (Breast cancers) and 0.6 ± 2.5 yrs. (Endometrial cancers). A prior surgical treatment (OR = 1.19; 95% CI 1.02-1.40) or radiotherapy (OR = 1.34, 95% CI 1.21-1.49) in the initial primary malignancy is associated with a &gt; 5years development of a subsequent ovarian malignancy. Black patients (OR = 1.63, 95% CI 1.39-1.92) have the worst survival even after controlling for disease stage and treatment modalities. Determinants of improved overall survival include White race, private insurance, age &lt; 45 years at first primary malignancy diagnosis, prior surgical therapy, and increased latency interval. A prolonged latency interval is associated with a 74% increase in survival (OR = 0.26; 95%CI 0.23-0.30). Conclusions: Determinants of improved survival among patients with subsequent ovarian cancers following a prior primary malignancy include White race, private insurance, and a prolonged latency interval of progression from an initial primary malignancy to a subsequent ovarian cancer.
A novel support vector machine to predict sentinel lymph node status in elderly patients with breast cancer.
Authors: Abbas Hassan, Nina Tamirisa, Puneet Singh, Anaeze Chidiebele Offodile, Charles E. Butler
Journal: Journal of Clinical Oncology (2022)

1560 Background: Routine sentinel lymph node biopsy in older breast cancer patients with favorable tumor biology is not recommended. However, cases must be evaluated on an individual basis to avoid under or over-treatment. Many nomograms have been developed to calculate the risk of nodal positivity, but machine learning (ML) is a novel tool that may improve the accuracy of nodal prediction. In this study, we developed a support vector machine (SVM) model to delineate factors indicative of sentinel lymph node positivity and refine individualized nodal risk assessment for this heterogeneous patient population. Methods: We conducted a single-institution comprehensive retrospective review of patients 70 years or older diagnosed with unilateral stage I–III primary breast cancer from January 2005 to January 2016. Patient data was partitioned into training and testing sets. A SVM model was developed to predict lymph node status using patients’ demographics, tumor stage, genetic profile, and imaging data. Primary outcome was model performance determined by area under the curve (AUC). Secondary outcomes were accuracy, sensitivity and specificity. Permutation feature importance (PFI) analysis and accumulated local effect (ALE) plots were used to evaluate significant predictors identified by the SVM. Results: We identified 1706 consecutive patients who met the study criteria with a mean age of 76±4.5 years. The plurality of patients were Caucasian (82%), had ER+ (86%), PR+ (70%), HER2- (87%) stage I (72%) breast cancer. Sixteen percent of patients (n = 271) had a positive sentinel lymph node biopsy. The SVM model demonstrated good discriminatory performance for predicting sentinel lymph node positivity with mean AUC of 0.70 (95%CI, 0.62-0.77), mean accuracy of 84% (95%CI, 80-88%), mean sensitivity of 61% (95%CI, 57-66%), and mean specificity of 62% (95%CI, 52-73%). PFI and ALE identified higher disease stage, younger age, family history of breast cancer, margin status, estrogen and progesterone receptor positivity as independently associated with high risk of sentinel lymph node positivity. Conclusions: The proposed ML model accurately identified sentinel lymph node status in older patients with breast cancer. This model holds promise for counselling patients as to the potential risk for node positive disease which may impact surgical and adjuvant therapy recommendations.
Sustainable multidisciplinary team referral for non-metastatic renal cell carcinoma: A survival-based recommendation
Authors: G. Basile, G. Rosiello, G. Fallara, A. Pellegrino, A. Larcher, D. Raggi, R. Campi, S.K. Pal, P.E. Spiess, F. Montorsi, T.K. Choueiri, A. Necchi, U. Capitanio
Journal: European Urology (2022)
ETMR-10. Retrospective molecular re-evaluation of CNS PNETs; a population-based study
Authors: Elizabeth Schepke, Maja Löfgren, Torsten Pietsch, Teresia Kling, Claes Nordborg, Thomas Olsson Bontell, Stefan Holm, Anders Öberg, Per Nyman, Marie Eliasson-Hofvander, Magnus Sabel, Birgitta Lannering, Helena Carén
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The heterogeneous group of tumors, primitive neuro-ectodermal tumors of the central nervous system (CNS-PNETs), is a group of rare childhood embryonal tumors associated with a poor prognosis. In recent years, molecular analyzes have shown that CNS-PNETs consist of high-grade gliomas (HGG), ependymomas, different embryonal entities like atypical teratoid /rhabdoid tumors (AT/RT), CNS neuroblastoma FOXR2 and embryonal tumor with multi-layered rosettes (ETMR). Each of these tumor types is unusual and long-term clinical follow-up data are sparse. METHODS: We retrospectively re-evaluated all children (0-18 years old) diagnosed with a CNS-PNET in Sweden during 1984-2015. In total, 88 supratentorial CNS-PNETs were identified in the Swedish Childhood Cancer Registry and from these formalin-fixed paraffin-embedded tumor material was available for 69 patients. All tumors were reviewed histopathologically by an experienced neuropathologist and were analyzed using genome-wide DNA methylation profiling and classified by the MNP brain tumor classifier. RESULTS: The largest entities, after re-evaluation, were HGG (30%), CNS NB-FOXR2 (12%), AT/RT (10%) and ETMR (8%). Some tumors were difficult to classify and will be further evaluated molecularly. Some examples: Best treatment results were seen for patients with CNS-NB FOXR2 (5-year PFS: 100%) where all patients had received craniospinal radiotherapy (CSI). Patients with ETMR were all very young and survival data show early progression and poor survival (5-year OS 34%). CONCLUSIONS: Although the patient material is relatively small, it is population-based with long follow-up times. Our findings are in line with other studies and shows that CSI is important for cure for CNS-NB FOXR2 and that intensive multi-modal therapies needs to be evaluated in up-front studies for these rare embryonal tumors.
Trends in the incidence of early-onset invasive colorectal cancer between 1990 and 2018, stratified by race/ethnicity, gender, and anatomic sub-sites among Pennsylvania residents.
Authors: Inimfon Jackson, Edward Bley, Michael Goldberg, Matthew Behme, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2022)

10543 Background: Recent data report a rising incidence of colorectal cancer in the younger population and epidemiological evidence is useful to enable clinicians understand evolving trends and better counsel patients on the potential risks/benefits of early screening. We explored the trends in incidence of early-onset invasive colorectal cancer by race/ethnicity, gender, and anatomic sub-sites. Methods: Repeated cross-sectional analyses were conducted among adults &lt; 50 years diagnosed with invasive colorectal cancer between 1990-2018 in Pennsylvania using data from the Pennsylvania Department of Health Cancer Registry. Temporal trends in invasive cancer with age adjusted incidence rates according to race/ethnicity, gender, and anatomical sub-sites were assessed using the Enterprise Data Dissemination Informatics Exchange (EDDIE). Results: 16,154 cases of early-onset invasive colorectal cancer were diagnosed between 1990 and 2018. There was an increased incidence of invasive colorectal cancer in the general population especially when stratified by gender, race/ethnicity and among those &lt; 40 years of age. While rates among Whites nearly doubled from 5.4 per 100,000 (95% Confidence Interval (CI): 4.9–6.0 per 100,000) population to 9.0 per 100,000 (95% CI: 8.2– 9.7 per 100,000) population, the rates in the Black population have been decreasing in recent years from a peak of 10.4 per 100,000 (95% CI: 8.4–12.7 per 100,000) population in 2011 to 7.3 per 100,000 (95% CI: 5.7–9.3 per 100,000) population in 2018. However, the Hispanic rates have remained stable. Across anatomical subsites, the rectum, rectosigmoid and sigmoid colon were found to have rising trends in incidence rates over time. Conclusions: There is increased awareness on the need for early diagnosis of colorectal cancer in the young Black population. However, we found trends toward increasing incidence rates among Whites while rates in the Black population are now decreasing. These findings accentuate the need for quality provider-patient communication during primary care visits with a goal to improve adherence to the new colorectal cancer screening guidelines regardless of race/ethnicity.
Demographics and treatment outcomes in patients with EBV<sup>+</sup> PTLD treated with off-the-shelf EBV-specific CTL under an ongoing expanded access program in Europe: First analyses.
Authors: Sylvain Choquet, Sridhar Chaganti, Ben Uttenthal, Patrizia Comoli, Ralf Ulrich Trappe, Anke Friedetzky, Baodong Xing, Xiaoming Li, Tobias Boy Polak, Laurence Gamelin, Jan-Henrik Terwey, Daan Dierickx
Journal: Journal of Clinical Oncology (2022)

7530 Background: Patients undergoing allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT) are at risk of developing Epstein–Barr virus driven post-transplant lymphoproliferative disorder (EBV + PTLD), a rare hematologic malignancy, which is often aggressive and life-threatening. Patients with relapsed or refractory (r/r) EBV + PTLD have few treatment options with poor outcomes, demonstrating a clear unmet medical need. Tabelecleucel is an investigational, off-the-shelf, allogeneic EBV-specific T-cell immunotherapy being studied in patients with serious EBV + diseases (NCT04554914 &amp; NCT03394365) that has demonstrated clinical benefit and favorable safety profile in the treatment of EBV + PTLD after failure of rituximab (R) ± chemotherapy (Prockop, EBMT 2021, ATC 2021, ASH 2021). Methods: Atara Biotherapeutics supports an ongoing expanded access program (EAP) in Europe for patients with EBV + diseases who have no other treatment options. Here we report demographics, efficacy and safety results of r/r EBV + PTLD patients following SOT or HCT who presented between Jul 2020 and Nov 2021 and consented to research. Results: A total of 48 EAP requests from 9 countries for patients with EBV + diseases were received. Twenty-two patients from 7 countries consented to this research: 16 EBV + PTLD and 6 EBV + non-PTLD. Of the 16 PTLD patients 15 received at least one dose of tabelecleucel. Overall, 9 out of 15 (60%) patients achieved a response as assessed by the treating physician, with 6 complete responses and 3 partial responses. Eight out of nine responses were seen after the first cycle. No adverse events were reported as related to tabelecleucel by the treating physician. Conclusions: The successful execution of this European EAP demonstrates the feasibility to deliver an off-the-shelf allogeneic EBV + T-cell therapy in time-sensitive clinical situations when no other treatment options exist. These data show clinically meaningful outcomes for patients with r/r EBV + PTLD post-SOT or post-HCT treated with tabelecleucel consistent with previously reported favorable safety and efficacy profile (Prockop, ASH 2021).[Table: see text]
Deep learning models of cognitive processes constrained by human brain connectomes
Authors: Yu Zhang, Nicolas Farrugia, Pierre Bellec
Journal: Medical Image Analysis (2022)

Decoding cognitive processes from recordings of brain activity has been an active topic in neuroscience research for decades. Traditional decoding studies focused on pattern classification in specific regions of interest and averaging brain activity over many trials. Recently, brain decoding with graph neural networks has been shown to scale at fine temporal resolution and on the full brain, achieving state-of-the-art performance on the human connectome project benchmark. The reason behind this success is likely the strong inductive connectome prior that enables the integration of distributed patterns of brain activity. Yet, the nature of such inductive bias is still poorly understood. In this work, we investigate the impact of the inclusion of multiple path lengths (through high-order graph convolution), the homogeneity of brain parcels (graph nodes), and the type of interactions (graph edges). We evaluate the decoding models on a large population of 1200 participants, under 21 different experimental conditions, acquired from the Human Connectome Project database. Our findings reveal that the optimal choice for large-scale cognitive decoding is to propagate neural dynamics within empirical functional connectomes and integrate brain dynamics using high-order graph convolutions. In this setting, the model exhibits high decoding accuracy and robustness against adversarial attacks on the graph architecture, including randomization in functional connectomes and lesions in targeted brain regions and networks. The trained model relies on biologically meaningful features for the prediction of cognitive states and generates task-specific graph representations resembling task-evoked activation maps. These results demonstrate that a full-brain integrative model is critical for the large-scale brain decoding. Our study establishes principles of how to effectively leverage human connectome constraints in deep graph neural networks, providing new avenues to study the neural substrates of human cognition at scale.